Phase 2a, single center, randomized, double-blind, study to evaluate the immunogenicity and safety of one single administration of OVX836 influenza vaccine at two dose levels (180µg or 480μg) given intramuscularly (IM), either as a booster or a primary vaccination in healthy adults previously administered with OVX836, Influvac Tetra® or placebo in the OVX836-002 (EudraCT number: 2019-002939-28) and OVX836-003 (EudraCT number: 2021-002535-39) studies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

OSIVAX Belgique

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

15 Oct 2024 → 2 Jun 2025

Decision date (initial)

2024-10-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516267-83-00

ClinicalTrials.gov

NCT06582277

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

To evaluate the reactogenicity and safety of a booster dose of OVX836 (180µg or 480µg) in subjects who previously received a primary OVX836 dose of 180µg to 480µg during the 2019/2020 or 2021/2022 winter seasons, versus control subjects who will receive a primary single dose of OVX836 480µg during this study.

Secondary objectives 1

1. To evaluate and compare the immunogenicity (humoral and cell-mediated immune responses) of a booster dose of OVX836 (180µg or 480µg) in subjects who previously received a primary OVX836 dose of 180µg to 480µg during the 2019/2020 or 2021/2022 winter seasons, versus control subjects who will receive a primary single dose of OVX836 480µg during this study.

Conditions and MedDRA coding

Influenza

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject who voluntarily provides written informed consent to participate in the study.
2. Healthy male or female subjects, as determined by medical history and medical examination.
3. Subject compliant with the reproductive criteria for male and female participants (refer to Appendix A).
4. Subjects who participated in the OVX836-002 (subjects having received OVX836 180µg or Influvac Tetra® only; EudraCT number: 2019-002939-28) or OVX836-003 (EudraCT number: 2021-002535-39) studies.
5. Subjects aged 20 and 64 years, inclusive.
6. Reliable and willing to commit to participating for the duration of the study, and capable of following study procedures diligently.
7. Ability and technical capability to complete an eDiary.

Exclusion criteria 24

1. Subjects with a body mass index (BMI) ≤18 kg/m² or ≥35 kg/m² on the day of vaccination.
2. Previous influenza vaccination within 6 months before the day of vaccination or planned to receive during the whole study period.
3. Previous vaccination with an mRNA-based influenza vaccine including NP in its composition.
4. Any known or suspected immunodeficient conditions.
5. Past or current history of significant autoimmune diseases, as judged by the Investigator.
6. Current history of uncontrolled medical illness such as diabetes, hypertension, heart, renal or hepatic diseases.
7. Known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
8. Pregnant or lactating woman.
9. Female planning to become pregnant or planning to discontinue contraceptive precautions until the end of the trial.
10. Participants with extensive tattoos covering deltoid regions on both arms that would preclude the assessment of local reactogenicity.
11. Other vaccination within 3 months prior to the day of study vaccination for live attenuated vaccines, or within 1 month prior to the day of study vaccination for non-live vaccines, at the exception of COVID vaccines which can be administered within 14 days before or after study vaccine administration.
12. Planning to receive other vaccines during the first 28 days following the study vaccine administration.
13. Administration of any investigational or non-registered drug or vaccine within 3 months prior to the administration of study vaccines, or planned administration of any such product during the entire study period.
14. History of receiving blood, blood components or immunoglobulins within 3 months prior to the day of vaccination or planned to receive such product during the whole study period.
15. Presence of an acute febrile illness on the day of vaccination (oral temperature >38.0°C, temporary exclusion criterion).
16. Past or current history of any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome.
17. Behavioral or cognitive impairment, or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject's ability to participate in the study.
18. History of alcohol or drug abuse that ceased less than 6 months before enrolment, current alcohol or drug abuse according to the Investigator’s judgement), smoking habit of more than 10 cigarettes /day, or current vaping (nicotine consumption corresponding to more than 10 cigarettes/day).
19. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting one month before the study vaccine administration. For corticosteroids, this will mean prednisone equivalent ≥20 mg/day. Inhaled, topical and intra-articular steroids are allowed.
20. Current or past malignancy, unless completely resolved for >5 years (except non-metastatic basal cell carcinoma which has been completely resected).
21. History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions to vaccines, or allergy to kanamycin or any other component of the vaccine.
22. Any contraindication to IM administration, as judged by the Investigator.
23. Individuals with a history of any illness that, in the opinion of the Investigator, could potentially interfere with the results of the study or pose additional risk to the subjects by participating in the study.
24. Sponsor employees or Investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted, including children of newly composed families.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Safety evaluation of OVX836 (180µg and 480µg): Number and percentage of subjects reporting solicited local and systemic symptoms within 7 days after vaccine administration.
2. Safety evaluation of OVX836 (180µg and 480µg): Number and percentage of subjects reporting unsolicited AEs within 29 days after vaccine administration.
3. Safety evaluation of OVX836 (180µg and 480µg): Number and percentage of subjects reporting SAEs during the entire study duration.
4. Number and percentage of subjects reporting ILIs and RT-PCR confirmed influenza A or B (overall and occurring more than 14 days post-vaccination, i.e., vaccine failure), RSV, SARS-CoV-2 and/or other respiratory infectious agents.

Secondary endpoints 7

1. Cell-mediated immune response to OVX836 (180µg and 480µg) in terms of NP-specific IFNγ spot forming cells frequencies in peripheral blood, measured by ELISPOT, at Days 8 and 29 versus pre-injection baseline (Day 1).
2. Frequencies of NP-specific CD4+ and CD8+T-cells expressing IL-2, TNFα and/or IFNγ, measured by flow cytometry, following in vitro stimulation of PBMC collected on Days 8 and 29 as compared to frequencies observed in PBMC collected at baseline, i.e. pre-injection on Day 1.
3. Cross-reactivity of the NP influenza-specific responses by IFNγ ELISPOT against selected circulating and emerging strains of influenza.
4. Geometric mean titers (GMTs) of anti-NP Immunoglobulin G (IgG) (ELISA, serum) at Days 8 and 29 versus pre-injection baseline (Day 1).
5. Number and percentage of subjects with an increase (two-fold and four-fold) in anti-NP IgG (ELISA, serum) titer at Days 8 and 29 versus pre-injection baseline (Day 1).
6. GMTs of anti-OVX313 tag (Oligodom®) IgG level (ELISA, serum) at Days 8 and 29 versus pre-injection baseline (Day 1).
7. Anti-C4bp (C4b-binding protein) oligomerization domain IgG titers (ELISA, serum) at Days 8 and 29 versus pre-injection baseline (Day 1), in subjects with positive result for anti-OVX313 (anti-OVX313 titer >12.5).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

OSIVAX Belgique

Sponsor organisation

OSIVAX Belgique

Address

Rue Des Chasseurs-Ardennais 7

City

Liege

Postcode

4031

Country

Belgium

Scientific contact point

Organisation

OSIVAX Belgique

Contact name

Florence Nicolas

Public contact point

Organisation

OSIVAX Belgique

Contact name

Florence Nicolas

Third parties 5

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications